ArticleHepatology (Baltimore, Md.)2018
MicroRNA (miR)-433 and miR-22 dysregulations induce histone-deacetylase-6 overexpression and ciliary loss in cholangiocarcinoma.
Article in Hepatology (Baltimore, Md.), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 74 citations in OpenAlex.
- Primary cilia: sensors of biliary homeostasis and disease.Nature reviews. Gastroenterology & hepatology · 2026Review
- Primary cilium as a sensory organelle and metabolic hub in health and diseases.Journal of biomedical science · 2026Review
- Primary ciliogenesis is promoted during epithelial-mesenchymal transition via a miR-200 - DZIP1 axis.Cell communication and signaling : CCS · 2026Article
- Primary cilia promote resistance to EGFR tyrosine kinase inhibitor, osimertinib, in non-small cell lung cancer.bioRxiv : the preprint server for biology · 2026Article
- The Evolving Landscape of microRNAs in Cholangiocarcinoma and Pancreatic Cancer.Diagnostics (Basel, Switzerland) · 2025Review
- Primary Cilia in Hepatic Biliary Hyperplasia: Implications for Liver Diseases.Seminars in liver disease · 2025Review
- Cholangiocytes' primary cilia regulate DNA damage response and repair.American journal of physiology. Gastrointestinal and liver physiology · 2025Article
- Reprogramming of fatty acid metabolism: a hidden force regulating the occurrence and progression of cholangiocarcinoma.Cell death discovery · 2025Review
- NAdvanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Tubulin Acetylation: A Critical Regulator of Microtubule Function.Results and problems in cell differentiation · 2025Review
- The miR-669a-5p/G3BP/HDAC6/AKAP12 Axis Regulates Primary Cilia Length.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Role of lipids in the control of autophagy and primary cilium signaling in neurons.Neural regeneration research · 2024Review
- Immunomodulatory potential of primary cilia in the skin.Frontiers in immunology · 2024Review
- Review
- miR-22 gene therapy treats HCC by promoting anti-tumor immunity and enhancing metabolism.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Integration analysis of miRNA-mRNA expression exploring their potential roles in intrahepatic cholangiocarcinoma.Scientific reports · 2023Article
- STIL/AURKA axis promotes cell proliferation by influencing primary cilia formation in bladder cancer.Journal of translational medicine · 2023Article
- HDAC6: A unique HDAC family member as a cancer target.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Review
- The role of MiRNA-433 in malignant tumors of digestive tract as tumor suppressor.Cancer reports (Hoboken, N.J.) · 2022Review
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13 authors at 5 institutions in 2 countries.
Funding
Abstract
Cholangiocytes normally express primary cilia, a multisensory organelle that detects signals from the cellular environment. Cilia are significantly reduced in cholangiocarcinoma (CCA) by a mechanism involving overexpression of histone deacetylase 6 (HDAC6). Despite HDAC6 overexpression in CCA, we found no differences in its mRNA level, suggesting a posttranscriptional regulation, possibly involving microRNAs (miRNAs). Here, we describe that at least two HDAC6-targeting miRNAs, miR-433 and miR-22, are down-regulated in CCA both in vitro and in vivo. Experimental restoration of these miRNAs in CCA cells reduced HDAC6 expression, induced ciliary restoration, and decreased the malignant phenotype. Furthermore, in contrast to the mature forms, levels of precursor forms of these miRNAs were higher in CCA compared to normal cholangiocytes and accumulated in the nuclei, suggesting a defective nuclear export. We assessed the expression of Exportin-5, the protein responsible for transporting miRNA precursors out of the nucleus, and found it to be reduced by 50% in CCA compared to normal cholangiocytes. Experimental overexpression of Exportin-5 in CCA cells restored precursor and mature forms of these miRNAs to normal levels, inducing a decrease in the expression of HDAC6 and a decrease in the malignant phenotype. Conversely, short hairpin RNA (shRNA) depletion of Exportin-5 in normal cholangiocytes resulted in increased nuclear retention of precursor miRNAs, decreased mature miRNAs, increased cell proliferation, and shorter cilia.
conclusionThese data suggest that down-regulated Exportin-5 impairs the nuclear export of miR-433 and miR-22 precursor forms, causing a decrease in levels of mature miR-433 and miR-22 forms, and leading to overexpression of HDAC6 and ciliary loss in CCA. (Hepatology 2018).
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.